tbuckley/cabot-search huggingface dataset:
FDA analysis of toxicity profiles of oral TKIs recently approved for non-small cell lung cancer based on receipt of prior immune checkpoint inhibitor therapy.
Authors: Yufan Liu, Elizabeth Duke, Nicole Lauren Drezner, Harpreet Singh, Paul Kluetz, Richard Pazdur, Erin A. Larkins
Journal: Journal of Clinical Oncology (2023)

9119 Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 are standard front-line therapy for advanced non-small cell lung cancer (NSCLC). Molecularly targeted tyrosine kinase inhibitors (TKIs) are standard of care for subsets of oncogene-driven NSCLC. Published literature suggests the possibility of increased toxicity in patients who receive ICIs followed by EGFR or ALK TKI treatment. However, the toxicity profile in patients who receive ICIs followed by TKIs with other genomic targets has not been well described. Methods: Marketing applications for TKIs in patients with NSCLC submitted to the Office of Oncologic Diseases between Jan 2019 to Dec 2022 were reviewed. Datasets were analyzed for demographics, treatment-emergent adverse events (TEAE), and prior anti-cancer therapies for TKI-treated patients in the primary efficacy population. Drug classes for which &lt; 5% of patients received prior ICI were excluded. Grade 3-4 TEAE, serious adverse events (SAE), discontinuation TEAE and TEAE of interest (hepatotoxicity, rash, and interstitial lung disease [ILD]) were summarized. Results: 9 applications were identified and 2 were excluded. The remaining applications involved TKIs targeting EGFR exon 20 insertion, KRAS G12C, MET exon 14 skipping, and RET fusion alterations. Analyses included 867 patients; 61% received prior ICI therapy. Patient characteristics and results of analyses are presented in the table. In our pooled analysis, the incidence of Grade 3-4 AEs, SAEs, and hepatotoxicity were slightly higher in the prior ICI group, while the incidence of discontinuation TEAE, ILD, and rash were similar between groups. Analysis for hepatotoxicity was limited to reported AEs (did not include analysis of laboratory data). Review of toxicity data across individual drug classes did not show major differences compared to the overall results. Conclusions: Our analysis of safety data for newer TKIs with varied genomic targets does not appear to show excessive toxicity in patients with NSCLC who received prior ICI compared to those who did not. In future clinical trials evaluating TKIs in this population, inclusion of patients who have received prior ICI therapy should be considered when appropriate. [Table: see text]
Modifiable risk factors and risk of colorectal and endometrial cancer in Lynch syndrome: A systematic review and meta-analysis.
Authors: Robert Power, Damien Doherty, Imelda Parker, Maeve Aine Lowery, Karen Anne Cadoo
Journal: Journal of Clinical Oncology (2023)

e22544 Background: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancer. Non-genetic risk factors, including obesity, physical activity, alcohol intake, and smoking are well-established in sporadic cancers but are less studied in Lynch syndrome. A better understanding of these risk factors could directly contribute to cancer prevention. Methods: Searches were conducted on MEDLINE, Embase and Web of Science for retrospective or prospective cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Screening, data extraction and quality assessment were completed by 2 reviewers independently. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for colorectal and endometrial cancer were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462) and the meta-analysis conducted in accordance with PRISMA and MOOSE reporting guidelines. Results: A total of 770 citations were reviewed. Twelve cohort studies involving 12685 patients with Lynch syndrome investigated risk of colorectal cancer, while 3 studies including 1865 patients assessed risk factors for endometrial cancer. Eight colorectal cancer studies were eligible for meta-analysis. Obesity (HR 2.38, 95% CI 1.52-3.73) and alcohol intake (HR 1.43, 95% CI 1.05-1.94) increased colorectal cancer risk, physical activity was protective (HR 0.66, 95% CI 0.52-0.83), and smoking had no effect (HR 1.02 95% CI 0.83-1.27). Type 2 diabetes mellitus and low dietary intake of calcium and multivitamins might increase risk of colorectal cancer, although more studies are needed. There is a paucity of data pertaining to endometrial cancer. In a qualitative synthesis of 3 endometrial cancer cohort studies, female hormonal risk factors and type 2 diabetes mellitus may affect the risk of endometrial cancer, but obesity was not associated with an increased risk. Conclusions: Lifestyle recommendations related to weight, physical activity, and alcohol may also be relevant to cancer prevention for individuals with Lynch syndrome and may provide a meaningful adjunct to standard interventions for risk modification. There are very poor data examining modifiable risk factors in endometrial cancer. Further high-quality prospective cohort studies, in particular including endometrial cancer as an endpoint, are needed to inform evidence-based cancer prevention strategies in this high-risk population.
Therapy preferences of patients with cancer.
Authors: Prajwal Dhakal, Christopher S. Wichman, Bunny J. Pozehl, Radowan Elnair, Amulya Yellala, Kalika Mahato, Vijaya Raj Bhatt
Journal: Journal of Clinical Oncology (2023)

e24205 Background: Clear understanding of patient (pt) preferences is crucial for creating a treatment (tx) plan that aligns with pt's goals and expectations. We developed "Therapy Preference Scale" (TPS), a self-reported questionnaire, to measure tx preferences of pts with cancer. TPS includes 30 questions: 19 questions on pt preferences on safety, efficacy, and other aspects of therapy (on scale of 0-10), 8 questions on importance of different aspects of tx (on 4-item Likert scale with choices of 'strongly disagree,' 'disagree,' 'agree,' and 'strongly agree.'), and 3 questions on intent of therapy, expenses, and life expectancy gain. This report presents results of the 8 questions rated on the 4-item Likert scale from a prospective study using TPS. Methods: 300 pts &gt; 18 yrs with a cancer diagnosis completed TPS. We divided pts into 4 groups: Male &lt; 60 yrs (M &lt; 60), Male ≥60 yrs (M ≥60), Female &lt; 60 yrs (F &lt; 60), and Female ≥60 yrs (F ≥60). We compared responses between M &lt; 60 and M≥60 and between F &lt; 60 and F≥60. The responses were categorized into 2 groups: "disagree" (combining "strongly disagree" and "disagree") and "agree" (combining "strongly agree" and "agree"). Results: Median age was 61 yrs (range 19-89). 62% had solid tumors. 57% indicated cure as their tx goal versus gain in life expectancy without cure (35%) or symptom relief (8%). 4 groups were 20% M &lt; 60, 32% M ≥60, 19% F &lt; 60, and 29% F ≥60. M &lt; 60 were more likely to accept tx with side effects and financial burden, while M ≥60 prioritized avoiding poor quality of life (QoL). F &lt; 60 were more likely to undergo tx causing significant pain, while F ≥60 would avoid permanent cognitive impairment. Table 1 shows percentage of pts who agreed with the 8 questions. Conclusions: Despite similar preferences for a cure, age and gender play role in prioritizing tx options, including those with potential side effects such as life-threatening infection, poor QoL, financial burden, severe pain, and permanent cognitive impairment. TPS can improve the precision medicine approach and aid in choosing the right tx for each pt. [Table: see text]
Nutrition assessment reports in oncology clinical trials.
Authors: Ye Myint Aung, Aynur Aktas, Vishal Shroff, Kunal C. Kadakia, Jake Waldman, Declan Walsh
Journal: Journal of Clinical Oncology (2023)

e24142 Background: Malnutrition is common in cancer and associated with greater treatment toxicity and poor clinical outcomes. Validated screening tools can identify individuals at risk; however, they are underutilized in clinical practice. It is also unclear how nutrition status is assessed and reported in oncology clinical trials. We analyzed nutrition assessment protocols in clinical trials published in major US oncology journals. Methods: Three researchers (YA, AA, VS) identified studies published in the Journal of Clinical Oncology, JAMA Oncology, and the New England Journal of Medicine under the “original reports”, “original articles”, or “’ research” categories, respectively (1/1/2022-12/31/2022). We selected studies that reported outcomes of systemic therapeutic interventions in any Phase clinical trial. This included chemotherapy, hormone therapy, and immunotherapy alone or combined with radiation therapy or surgical procedures. Systematic reviews, meta-analyses, commentaries, retrospective studies, and secondary analyses of pooled data from completed trials were excluded. Descriptive statistics summarized how malnutrition risk was assessed and nutrition data reported. Results: 521 articles were reviewed; 153 (29%) studies met eligibility criteria. Most were randomized trials (103/153, 67%) and Phase II or III (126/153, 82%). Malnutrition risk assessment was absent from all studies. Overall, 15/153 (10%) reported either baseline Body Mass Index or pre-treatment weight changes. These variables were included in the survival analysis of 5/15 studies. The primary cancer sites studied were breast (5/15), gynecologic (3/15), hematologic (3/15), multiple sites (2/15), prostate (1/15), and pancreatic (1/15). Conclusions: Most oncology clinical trials ignore and/or underreport nutrition status. Only 10% of the studies reported nutrition status data, and not all cancer sites were represented. There is a need to routinely assess nutrition status and (given the major prognostic value) investigate its potential uses for patient selection and stratification in clinical trials.
The CROWN study (CaRdiac outcomes with near complete estrogen deprivation): A multicenter, prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor.
Authors: Emily H. Douglas, Carolyn J. Park, Nathaniel S. O'Connell, Katherine C. Ansley, Karl M. Richardson, Susan Faye Dent, Mary Helen Helen Hackney, Ralph D'Agostino, W. Gregory Hundley, Jennifer H. Jordan, Alexandra Thomas
Journal: Journal of Clinical Oncology (2023)

TPS12142 Background: Treatment for premenopausal women with high or intermediate risk hormone receptor (HR)+ breast cancer (BC) now includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV disease. Taken together with the CV morbidity associated with other aspects of BC treatment and the future life-years of these women, the CV impact of NCED warrants further study. The CROWN study will use sophisticated imaging assessments of cardiac dysfunction to understand the evolution of CV injury, as well as biomarker and demographic correlates, with the goal of developing tools to assess and mitigate CV risk. Methods: This is a NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Atrium Health Wake Forest Baptist, Virginia Commonwealth and Duke) that will include premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-1. HR+ BC patients will receive an AI and OFS. Women with HR- BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table 1). These assessments will include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. We will correlate CMR imaging with CCTA to provide complementary detail of coronary plaque changes. The study will also assess the relevance of pre-existing risk factors on study outcomes, including an emphasis on racial disparities, and dynamic change in modifiable and treatment related risk factors. We plan to enroll 90 women, 67 in the NCED group and 23 in the HR-group, allowing for a 10% drop out rate. There are two primary types of statistical analyses. The first includes testing hypotheses between group (NCED vs HR-) and within group (longitudinal changes within the NCED group). The second analyses, involve developing predictive equations utilizing a stepwise linear regression approach to determine if patient demographics, clinical parameters and serum biomarkers are associated with cardiovascular changes over time. Present accrual is 4. Clinical trial information: NCT05309655 . [Table: see text]
Quality for all: Clinical trial enrollment and end-of-life care in solid and hematologic malignancies.
Authors: Melissa R Rosen, Katherine A Lambert, Morgan Megumi Nakatani, Salam Ibrahim, Tracy Troung, Kelvin Feng, Chloe Fournier, Arif Kamal, Thomas William LeBlanc, Laura J Havrilesky, Brittany Anne Davidson
Journal: Journal of Clinical Oncology (2023)

12028 Background: All patients with cancer deserve quality end-of-life (EOL) care.Despite established EOL quality metrics, many patients with cancer receive futile, aggressive EOL care with infrequent palliative care involvement and advanced care planning (ACP) documentation. Clinical trials are critical to advancing cancer care; at National Cancer Institute-designated cancer centers, ~20% of patients participate in clinical trials at some point. We aim to identify associations between trial enrollment in the last year of life (YOL) and EOL quality metrics for adults with solid or hematologic malignancies to identify opportunities to advance cancer care near death. Methods: This is a retrospective review of patients with solid or hematologic cancers treated at a single academic institution who died of disease between 2018 – 2022. Patients were identified using institutional registries. Inclusion criteria were ≥18 years of age with active disease at death. Outcomes include: initiation of new anti-cancer therapy, Intensive Care Unit (ICU) admission, hospitalization, or Emergency Department (ED) visit in the last 30 days of life (DOL), referral to hospice, palliative care involvement, and documentation of goals of care (GOC) and ACP paperwork. Results: Among 9,384 patients, 637 (6.8%) enrolled in clinical trials in the last YOL. Most common disease sites were gastrointestinal, thoracic, and genitourinary. Patients enrolled in clinical trials were more likely to initiate new anti-cancer treatments in the last 30 DOL (p=&lt;0.001), less likely to be referred to palliative care (p=0.008) or have GOC documentation (p=&lt;0.001), and less likely to visit the ED (p=0.016) or die in an inpatient setting (p=0.02). No differences were noted in referrals to hospice, ICU or hospital admissions in last 30 DOL, or ACP paperwork. Conclusions: Enrollment in a clinical trial in the last YOL was associated with several measures of aggressive EOL care. Low rates of palliative care and hospice engagement and infrequent documentation of ACP decisions across the study population suggest opportunities for improvement for all patients, regardless of trial enrollment. [Table: see text]
Large versus limited molecular profiling panel screening program in patients with metastatic sarcoma: An exploratory subgroup analysis from the ProfiLER 02 trial.
Authors: Mehdi Brahmi, Olivier Tredan, Nicolas Penel, Christine Chevreau, Christophe Perrin, Nelly Firmin, Emmanuelle Bompas, Francois Bertucci, Valéry Attignon, Pierre Saintigny, Isabelle Treilleux, Sylvie Chabaud, Gwenaelle Garin, David Pérol, Jean-Yves Blay, Armelle Dufresne
Journal: Journal of Clinical Oncology (2023)

11545 Background: Profiler 02 (NCT03163732) is a multicentre, randomized molecular screening clinical trial aiming to evaluate the feasibility and the benefit of a large NGS (Next-generation sequencing) panel (FoundationOne Medicine NGS panel or FOne, 324 cancer-related genes) compared to a limited one (Control panel or CTRL, 87 cancer-related genes) in terms of clinical, quality of life and health economic outcomes. We present here the results of the patients with advanced/metastatic sarcoma included in the Profiler 02 trial. Methods: Patients (pts) were enrolled during their first-line of standard therapy for an advanced sarcoma. All sarcomas diagnosIs were performed within the RRePS network (French pathology network of reference for sarcomas) and a central pathological review confirmed if quality and quantity of material were acceptable for molecular analysis. Patients were randomized within the two study arms (FOne versus CTRL) and DNA was analysed using both panels. The primary objective of the study was to compare the proportion of patients for whom a genomically driven recommended therapy (RT) could be initiated based on the FOne versus CTRL panels. A dedicated Molecular Tumour Board (MTB) reviewed tumour genomics data of both panels independently to propose a RT. Results: From January 2018 to July 2019, 39 pts with sarcoma (20F, 19M), with a median age of 54 years [21-81], were randomized between FOne Arm (17 pts) and CTRL Arm (22 pts). Pathological subtypes per arm are presented in the the table. Overall, 19 pts (49%) had at least one genomically driven RT, 11 according to both panels and 8 according to FOne panel exclusively (McNemar’s test, p=0.01). Main RT were CDK4/6 inhibitors ( n=5), PI3K/AKT/mTOR inhibitors ( n=4), and immunotherapy ( n=4). After the MBT, a RT was initiated for seven patients, four according to FOne panel only and three according to both panels. Importantly, a complete response was observed for a metastatic MPNST (Malignant Peripheral Nerve Sheath Tumor) with a high tumour mutational burden (TMB) detected by the FOne panel (37 mutations per megabase) and treated with durvalumab (anti-PDL1) + tremelimumab (anti-CTLA4). Conclusions: Although from an exploratory subgroup analysis, these results suggest that a large molecular profiling panel including TMB (FOne panel) might increase the number of RT and the number of sarcoma patients treated. Studies of precision medicine in rare cancers such as sarcomas are feasible,this approach could benefit to patients. Clinical trial information: NCT03163732 . [Table: see text]
Frequency and patterns of TP53 mutations in lung cancer.
Authors: Yaxian Yang, Heran Wang, Lucas Wang, WenTao Fan, Bin Lian, Ying Jin, Weiquan Luo, Jiewei Mao, Yilin Feng, Hongtao Xie, Mingjian Huang, Liyu Zheng, Zhaodong Pan, Mingming Huang, Yongsi Wang, Yunjie Wen, Jian Huang
Journal: Journal of Clinical Oncology (2023)

e21013 Background: Lung cancer (LC) is the second leading causes of cancer-related mortality and composed of diverse molecular types. Tumor suppressor gene TP53 is one of the most frequency mutation genes in cancer, however, whether there are the hot sports of TP53 mutations has always been a challenging issue. The aim of this study was to explore the spectrums and hot spots of TP53 mutation in LC. Methods: The total 1932 LC tissue samples (from same number of patients，all cases had patients' informed consent) in formalin fixed and paraffin embedded were collected from Guangzhou Huayin Health Medical Group Co.,Ltd. By targeting next generation sequencing (NGS) of 600 genes, the mutation information of TP53 and other genes was obtained. Results: Among 1932 samples, 1025(53%) were male, 1685(87.2%) were lung adenocarcinoma (LUAD), 232(12.0%) were lung squamous cell carcinoma (LSCC), 7(0.4%) were large-cell carcinoma and 8(0.4%) were small-cell carcinoma, median age was 62.82(range: 27-92). The mutated TP53 was detected in 890 (46%) samples. Other most frequently altered genes were EGFR (1114/1932, 57%), KRAS (213/1932, 11%), PIK3CA (116/1932, 6%), APC (107/1932, 6%) and ERBB2 (97/1932, 5%) . Additionally, 412 (21.3%) patients with TP53 and EGFR co-mutation, TP53 and KRAS co-mutation occurred in 81 (4.2%) patients, PIK3CA mutation co-occurred with TP53 in 53 (2.7%) patients. The total of 920 TP53 mutant sites were detected, and these sites scattered throughout the 11 exons, especially exon 5-8. 13 of these mutation sites which accounted as high frequency ( &gt; 10), including R273C (18/920), R248W (16/920), Y220C (15/920), Y163C (14/920), R249S (13/920), R282W (13/920), H179R (12/920), R158L (12/920), R175H (11/920), G245D (11/920), R273H (10/920), Y234C (10/920), and R273L (10/902). In addition, missense mutations were the main type, and the proportion of SNP with C &gt; T was the highest in mutation sites. Conclusions: This study characterized the mutational signatures that TP53 mutations are interspersed, and hot spots are just in small proportions in LC. This study may provide a basis for drug development for targeting TP53 mutations in the future.
Barriers and facilitators to discussion of cancer clinical trials: A qualitative study.
Authors: Brenda Sofia Castillo, Leigh Boehmer, Randall A. Oyer, Lori J. Pierce, Nadine Barrett, Carmen Guerra
Journal: Journal of Clinical Oncology (2023)

e18588 Background: NCCN guidelines indicate that cancer clinical trials (CCTs) are the best management for patients with cancer. However, only 5% of patients enroll in CCTs. Few studies have examined oncology providers’ perceptions of the barriers and facilitators to discussing CCTs. Methods: This qualitative study was part of the ASCO-ACCC Initiative to Increase Racial and Ethnic Diversity in Clinical Trials. A convenience sample of 10 U.S oncology providers participated in this sub-study. Their perceived barriers and facilitators to discussion of CCTs at the provider, patient, system, and CCTs levels were examined. To achieve triangulation, each provider reviewed 5 recent patient encounters to identify actual barriers and facilitators using chart-stimulated recall (CSR). Results: Nine participants were oncologists and 1 was a clinical research coordinator; 5 were female; 4 were White; 3 were Asian and 3 were Black. The table shows the most cited barriers and facilitators to discussion of CCTs, and the number of interviews in which those barriers or facilitators was mentioned. Barriers were patients’ negative attitudes and lack of knowledge of CCTs, provider assumptions about patients, lack of time to discuss CCTs and restrictive CCT eligibility criteria. Facilitators were having a CCT workforce, systematically discussing CCTs with all patients, patients requiring new treatment options or were aware of CCTs, and electronic medical record (EMR) strategies. CSR validated the most cited barriers and facilitators except patient negative attitudes and system barriers and facilitators. Conclusions: Many of the barriers to discussing CCTs are addressable with the cited facilitators (e.g. assumptions can be addressed by systematically discussing CCTs with all patients; lack of time to discuss CCTs can be addressed by a robust CCT workforce; restrictive CCT criteria can be broadened). A larger study is needed to further generalize and validate the findings. [Table: see text]